Currently, breast cancer is one of the prevalent malignancies in women, and mainly has two characteristics. First, with the increasing seriousness of pollution in human survival environment, the incidence rate of breast cancer shows remarkable rising tendency, and has become the first of female malignancies; second, with the widespread use of modern diagnosis and treatment techniques, more and more breast cancer patients can be found in time at the early stage of outbreak, and life cycles of the breast cancer patients are prolonged by advanced treatment methods so that the death rate decreases significantly. Through a hundred years of exploration and development of treatment methods of breast cancer, by so far, there are four main approaches for clinical treatment of breast cancer: operation, radiotherapy, chemotherapy and endocrinotherapy (operative therapy and drug treatment). In particular, the establishment of endocrine drug therapy results in a breakthrough in the breast cancer treatment.
In 1970s, the appearance of tamoxifen on the market consolidates a landmark in endocrine drug treatment of breast cancer. In 1990s, due to the appearance of third-generation aromatase inhibitor (AIs), the endocrine drug treatment of breast cancer enters a new era. Currently, the typical clinical drugs include tamoxifen (TAM), toremifene (TOR), raloxifene, anastrozole (rimidex), letrozole (femara), exemestane (aromasin), and estrogen inhibitor fulvestrant and relevant derivatives thereof. Fulvestrant is an excellent representative thereof, which is a unique antiestrogenic drug that has completed full clinical trials at first. As compared to TAM, its affinity to a receptor (ER) is 100 times higher, without action to weaken estrogen. This drug was approved by U.S. FDA on April, 2002. In 2007, Perey et al., Swiss scholars, reported the experiment results of Phase II trial of SGCCRT. They stated that there was no significant difference between fulvestrant and exemestane used respectively as replacement drugs for treating advanced breast cancer patients (postmenopausal) having experienced treatment failure of first-line non-steroid drugs in terms of overall response rate (37% vs 28%), clinical benefit rate (CBR) and side effects. This indicates that fulvestrant can be used as a drug for treating advanced breast cancer patients (postmenopausal) having experienced treatment failure of first-line non-steroid drugs. Currently, the fulvestrant injection applied in clinic was developed by Astrazeneca Co., under the trade name of FASLODEX, which entered the Chinese market in 2010. The formula thereof mainly used ethyl alcohol and benzyl alcohol as cosolvents, and benzyl benzoate and castor oil as dispersants, and had many adverse events in clinical use.
Lactate compounds are mostly ester substances generated by reaction of lactic acid and hydroxyl-containing compounds. Currently, the liquid compounds which are useful in pharmaceutical industries mainly include ethyl lactate, propyl lactate, butyl lactate and isopentyl lactate, and ethyl lactate is favorite because of weakest irritation.
Ethyl lactate, also named ethyl α-hydroxylpropionate, a colorless transparent liquid having formula C5H10O3, is an important raw material for medication production. Ethyl lactate is non-toxic, well soluble, non-volatile, fruity and easily biodegradable and soluble in water, alcohols, ethers, ketones and some oils (esters), and it is a substitute for toxic solvents (halogenated hydrocarbons, ethers) widely used in current pharmaceutical industries. In traditional pharmaceutical industries, ethyl lactate can be used as a lubricant for compressed tablets and an intermediate of pindolol drugs, and also can be used for transdermal formulations and injective formulations (“Manual of Latest National Standards of Pharmaceutic Adjuvants”, Sangui XIAO et al., 2006, P590). Therefore, ethyl lactate is worthy of development in pharmaceutical industries, and is a “green solvent” with a good prospect of application. The invention is mainly to develop an oily formulation for intramuscular injection using lactates as a cosolvent for fulvestrant or relevant derivatives thereof.